Widespread physical inactivity and resultant increases in cardiovascular and metabolic disease is a serious public health concern in the developed World. Unsurprisingly, the vast majority of research evidence suggests that physical activity is an effective intervention in addressing this state of affairs. An apparently strong case exists for the widespread clinical prescription of physical activity (PA). The application of PA in both preventative and remedial health is often termed ‘exercise is medicine’. Whilst on the basis of a large volume of laboratory data there is some consensus regarding the optimal delivery of health related PA, there is an apparent discrepancy between data emanating from laboratory and/or clinical studies and those emanating from real world interventions. In short, real world interventions do not appear to be as effective in promoting health as laboratory research suggests should be the case. This situation is compounded by a relative paucity of peer reviewed research studies reporting real world PA research, and furthermore by even less clinically relevant data. On this basis, a clear picture of the degree of translation from laboratory to the field is not yet possible. It is however not unreasonable to argue that the setting of the vast majority of research studies investigating the exercise is medicine hypothesis - that is laboratories, hospitals and clinics – might theoretically limit the translation of these findings to real world public health settings, and on that basis, more real world research is warranted. In Chapters 1 and 2 of this thesis the above arguments are developed into a case for a large scale ecologically valid translational study to investigate the effects of exercise on clinically relevant health variables. Chapter 3 presents the results of a pilot study that assessed the comparative effectiveness of structured PA (STRUC), unstructured PA (FREE), and PA counselling (PAC), among sedentary individuals in a community fitness centre setting. Significant improvements were observed in cardiovascular risk factors in all three groups, with no significant between-group differences. Chapters 4, 5 and 6 report data from a large scale, ecologically valid, longitudinal (48 week), multi-centre (n=26) investigation comparing the three interventions above with a measurement only condition. Participants were 1146 previously sedentary individuals. The ecological validity of the exercise is medicine hypothesis was tested from a clinical (Chapter 4) and behavioural (Chapter 5) perspective. Survey data pertaining to factors influencing the effectiveness of the interventions are explored in Chapter 6. Data suggest that the baseline health status of participants mediated effects over time, with participants most at risk of cardiovascular disease experiencing clinically significant improvements in health (e.g. VO2max: STRUC High -7.52% vs Low 32.03% (P=0.005), FREE High -4% vs Low 24.31% (P=0.023), PAC High -8.19 vs Low 35.8% (P=0.007), COM High -5.22% vs Low 8.17% (P=0.663)). These effects differed by condition. Improvements in body composition and VO2max following STRUC are consistent with previous laboratory findings. However, behavioural data indicate a stark contrast between retention rates observed in the current study and those reported elsewhere in laboratory studies (STRUC 34%, FREE 34%, PAC 29%, COM 31%). Post intervention survey data suggest that engaging with previously sedentary and/or low fitness participants within a fitness facility is challenging, and that as a consequence necessary levels of communication and motivation can be difficult to maintain. Overall data highlight several factors that differ between laboratory research and real world practice. These collectively potentially reduce the ecological validity of the exercise is medicine hypothesis. It is suggested that more real world research is warranted to better identify factors that might both mediate and moderate the relationship between physical activity and health.